IL-17-producing γδ T cells protect against Clostridium difficile infection

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Clostridium difficile infection (CDI) causes significant morbidity and mortality, particularly post-antibiotic use.
• Infant immunity against CDI and the role of immune mediators are not fully understood, with inflammation potentially being protective or pathogenic.

Purpose of the Study:

• To investigate the role of Interleukin-17A (IL-17A) produced by gamma delta (γδ) T cells in host defense against C. difficile infection.
• To elucidate the mechanisms underlying infant resistance to C. difficile colitis.

Main Methods:

• Analysis of fecal extracts from children with CDI for IL-17A and T cell receptor γ chain expression.
• Induction of IL-17 production by intestinal γδ T cells in infected mice.
• Assessment of C. difficile-induced inflammation and mortality in mice deficient in IL-17A or γδ T cells.
• Evaluation of neonatal mouse resistance to CDI following γδ T cell or IL-17A manipulation.

Main Results:

• Fecal samples from children with CDI showed elevated IL-17A and γδ T cell receptor expression.
• Intestinal γδ T cells efficiently produced IL-17A in response to C. difficile infection in mice.
• Mice lacking IL-17A or γδ T cells exhibited increased inflammation and mortality from CDI.
• Neonatal mice, possessing abundant IL-17-poised γδ T cells, were resistant to CDI, a resistance abrogated by γδ T cell or IL-17A depletion.

Conclusions:

• IL-17A-producing γδ T cells play a critical role in host defense against C. difficile infection.
• The expanded population of IL-17-producing γδ T cells in neonates confers resistance to C. difficile colitis.
• These findings provide a mechanistic basis for the observed resistance of infants to CDI.